Ayurveda practitioners take a holistic view of human disease. It views any disease as a dysfunction of the whole body rather than of a single organ or physiological process. Most of the Ayurvedic drugs therefore are likely to act on a number of dysfunctions of the body involving a number of organs and functions. In the 1960s the oleogum resin (gum guggul), isolated from a small tree Commiphora wighitii belonging to the family Burseraceae, was studied for its potential use in the treatment of elevated blood cholesterol or hyperlipidemia. The Commiphora tree, in general, is mentioned in the classic Ayurvedic literature for use in the treatment of bone fractures, arthritis, obesity, inflammation, cardiovascular diseases and lipid disorders. With the discovery of the hypolipidemic activity for the gum guggul, several chemical investigations were undertaken and found that gum guggul is a complex mixture of various classes of chemical compounds such as linans, lipids, diterpenoids, and plant steroids. Based on the structure function analysis of gum guggul, it was determined that the soluble portion of the gum in ethyl acetate, and specifically its neutral portion, contained most of the hypolipidemic properties. The neutral fraction was found to be source of sterol compounds known as Z- and E-guggulsterone, present in an amount minimum of 2.5% and responsible for lowering of blood cholesterol [Indian Pharmacopea, 1988; G. V. Satyavati, Economic and Medical Plant Research. 5, 47 (1991)].
Modern pharmacological studies on the crude drug and some of its fraction have supported the claims of Ayurveda. The anti-arthritis and anti-inflammatory activities were confirmed by Gujral et al. [M. L. Gujral, K. Sareen, K. K. Tangri, M. K. P. Amma, and A. K. Roy, Ind. J Physiol. Pharmacol. 4, 267 (1960)]. A mixed type of mechanism has been implicated for lipid lowering effect of gum guggul. The stimulation of plasma LCAT, hepatic lipases, receptor mediated catabolism of LDL and increased faecal bile acid excretion as well as suppression of hepatic cholesterol biosynthesis are the mechanisms responsible for lipid lowering effect of gum guggul [S, Nityanand and N. K. Kapoor, Ind J Exp. Biol. 11, 395 (1973); N. K. Kapoor and S, Nityanand, Ind. J Heart Res. Supp-1.22 (1988)]. With the discovery of the hypolipidemic activity for the gum resin, systemic chemical investigations were carried out to characterize compounds of the gum resin responsible for hypolipidemic activity. Mc Cook et al. have claimed alcoholic extract of gum guggul for controlling or preventing sebum secretion from sebocytes which is associated with a shiny, undesirable appearance and a disagreeable tactile sensation [J. P. Mc Cook et al. U.S. Pat. No. 5,690,948 (1997)].
As is already known, cholesterol is the precursor of neurosteroid pregnenlone. Similarity among biogenic precursor of pregnenolone and guggulsterones or guggulsterol [V. D. Patil, U. R. Nayak, and Sukh Dev, Tetrahedron 28, 2341 (1972)] has prompted exploration of the properties of synthetically pure pharmaceutically active novel phospholipid bonded to guggulsterone or guggulsterol. Behavioral studies have suggested a potential role of pregnenolone for memory enhancement. Intracerebroventricular (i.c.v) administration of pregnenolone and pregnenolone sulfate leads to amelioration in various memory tasks in rodents [J. F. Flood, J. F. Moorley, and E. Robert. Proc. Natl. Acad. Sci. USA 89, 1567 (1992)]. These memory-enhancing effects might be attributed to the N-methyl-D-aspartate (NMDA)-antagonistic properties of pregnenolone sulfate since NMDA agonists have been shown to impair cognitive functions in rodents [M. R. Bowlby, Mol. Pharmacol. 43, 813 (1993)].
In recent years, interest is increasing to understand the role of free radical oxidative damage in human diseases. Free radicals are highly reactive species that have the potential to oxidize biological membranes including proteins, lipids and DNA. To prevent or reduce oxidation, rich arrays of natural antioxidant mechanism exist. These antioxidant defense mechanisms have been found defective in many diseases. Increased production of free radicals has been strongly implicated in the pathophysiology of diabetes and atherosclerosis. Glucose combines with serum proteins and lipoproteins in a non-enzymatic glycation reaction and may auto oxidize in situ, generating free radicals and causing local oxidative damage [J. V. Hunt and S. P. Wolff, Free Radical Res. Commun. 12-13, 115 (1991)]. The free radical scavenging antioxidants react preferentially with free radicals before vital structure can be attacked. The gum guggul and E- and Z-guggulsterones are also known as to have antioxidant property [K. Singh, R. Chander, and N. K. Kapoor, Phytotherapy Research, 11, 291 (1997)].
The guggulphospholipid methods and compositions of the present invention find application in each of these areas.